The present invention is directed to a method of modulating permeability of the blood brain barrier using transcranial magnetic stimulation (TMS).
The blood-brain barrier (BBB) is a separation of circulating blood from the brain extracellular fluid in the central nervous system (CNS). It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. The BBB prevents the entry of substances that are hydrophilic or possess a high molecular weight. Its purpose is mainly to protect the brain from the entry of toxins and bacteria. However, it also acts as an impermeable barrier to the entry of more than 95% of the most clinically useful neurotherapeutic agents.
A number of experimental approaches have been proposed to open the BBB. These include high-intensity focused ultrasound, magnetic nanoparticles, peptide carriers, photodynamic therapy and electrochemotherapy. However, many of these techniques are highly speculative and are still in the experimental stages of development. Similarly, a number of techniques exist for the local administration of drugs to brain tumors. These include inter-cerebral implantation (for example, gliadel wafers), intra-arterial drug administration and hyper-osmotic disruption. However, the efficiency of these techniques is doubtful, and the implementation is often non-localized and invasive.
There are a number of important circumstances in which a means of safe and controlled blood brain barrier disruption (BBBD) would be of great clinical significance. These include the treatment of tumors of the central nervous system (CNS) in which a transient opening of the BBB could permit the delivery of chemotherapeutic agents to the brain during the window of BBB disruption with a potentially huge impact on the treatment of cancerous tumors of the CNS. Similarly, a number of diseases such as epilepsy and auto-immune diseases such as multiple sclerosis are characterized by unwanted breaches in BBB patency which would benefit from a means to reduce the permeability of the BBB. A goal of controlled BBB disruption therefore includes both a means to increase and decrease the permeability of the BBB.
Thus, it would be highly advantageous to have a method for blood brain barrier permeability control, which is safe, non-invasive, focused and reversible.